Background: A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. Methods: This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. Results: Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had -diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction –0.7 g/L, 95% CI –1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ –9.1 mg/L, 95% CI –14.4 to –3.7; kappa-FLC: Δ –5.7 mg/L, 95% CI –9.8 to –1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores. Conclusions: Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition. Trial Registration: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.

1.
USRDS report. Epidemiology of kidney disease in the United States.; 2018.
2.
Evans RW, Manninen DL, Garrison LP Jr, Hart LG, Blagg CR, Gutman RA, et al. The quality of life of patients with end-stage renal disease.
N Engl J Med
. 1985 Feb;312(9):553–9.
3.
Pecoits-Filho R, Lindholm B, Stenvinkel P. The malnutrition, inflammation, and atherosclerosis (MIA) syndrome – the heart of the matter.
Nephrol Dial Transplant
. 2002;17 Suppl 11:28–31.
4.
Wolley M, Jardine M, Hutchison CA. Exploring the Clinical Relevance of Providing Increased Removal of Large Middle Molecules.
Clin J Am Soc Nephrol
. 2018 May;13(5):805–14.
5.
Boschetti-de-Fierro A, Beck W, Hildwein H, Krause B, Storr M, Zweigart C. Membrane Innovation in Dialysis.
Contrib Nephrol
. 2017;191:100–14.
6.
Kirsch AH, Lyko R, Nilsson LG, Beck W, Amdahl M, Lechner P, et al. Performance of hemodialysis with novel medium cut-off dialyzers.
Nephrol Dial Transplant
. 2017 Jan;32(1):165–72.
7.
García-Prieto A, Vega A, Linares T, Abad S, Macías N, Aragoncillo I, et al. Evaluation of the efficacy of a medium cut-off dialyser and comparison with other high-flux dialysers in conventional haemodialysis and online haemodiafiltration.
Clin Kidney J
. 2018 Oct;11(5):742–6.
8.
Krishnasamy R, Hawley CM, Jardine MJ, Roberts MA, Cho YJ, Wong MG, et al. Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients.
BMC Nephrol
. 2018 Apr;19(1):89.
9.
Watanabe SM, Nekolaichuk C, Beaumont C, Johnson L, Myers J, Strasser F. A multicenter study comparing two numerical versions of the Edmonton Symptom Assessment System in palliative care patients.
J Pain Symptom Manage
. 2011 Feb;41(2):456–68.
10.
Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al.; International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome.
Sleep Med
. 2003 Mar;4(2):121–32.
11.
Johnson DW, Pascoe EM, Badve SV, Dalziel K, Cass A, Clarke P, et al.; HERO Study Collaborative Group. A randomized, placebo-controlled trial of pentoxifylline on erythropoiesis-stimulating agent hyporesponsiveness in anemic patients with CKD: the Handling Erythropoietin Resistance With Oxpentifylline (HERO) trial.
Am J Kidney Dis
. 2015 Jan;65(1):49–57.
12.
Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease.
Eur Respir J
. 2014 Dec;44(6):1428–46.
13.
Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH. A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.
Am J Kidney Dis
. 2001 Dec;38(6):1251–63.
14.
Pifer TB, McCullough KP, Port FK, Goodkin DA, Maroni BJ, Held PJ, et al. Mortality risk in hemodialysis patients and changes in nutritional indicators: DOPPS.
Kidney Int
. 2002 Dec;62(6):2238–45.
15.
Hutchison CA, Harding S, Mead G, Goehl H, Storr M, Bradwell A, et al. Serum free-light chain removal by high cutoff hemodialysis: optimizing removal and supportive care.
Artif Organs
. 2008 Dec;32(12):910–7.
16.
Zickler D, Schindler R, Willy K, Martus P, Pawlak M, Storr M, et al. Medium Cut-Off (MCO) Membranes Reduce Inflammation in Chronic Dialysis Patients-A Randomized Controlled Clinical Trial.
PLoS One
. 2017 Jan;12(1):e0169024.
17.
Masakane I, Sakurai K. Current approaches to middle molecule removal: room for innovation.
Nephrol Dial Transplant
. 2018 Oct;33(suppl_3):iii12–21.
18.
Roumelioti ME, Trietley G, Nolin TD, Ng YH, Xu Z, Alaini A, et al. Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis modalities: a meta-analysis of published studies.
Nephrol Dial Transplant
. 2018 Mar;33(3):542.
19.
Reque J, Perez Alba A, Panizo N, Sanchez-Canel JJ, Pascual MJ, Pons Prades R. Is Expanded Hemodialysis an Option to Online Hemodiafiltration for Small- and Middle-Sized Molecules Clearance?
Blood Purif
. 2019;47(1-3):126–31.
20.
Maduell F, Rodas L, Broseta JJ, Gomez M, Xipell M, Guillen E, et al. Medium Cut-Off Dialyzer versus Eight Hemodiafiltration Dialyzers: Comparison Using a Global Removal Score.
Blood Purif
. 2019;48(2):167–74.
21.
Davison SN, Jhangri GS, Johnson JA. Cross-sectional validity of a modified Edmonton symptom assessment system in dialysis patients: a simple assessment of symptom burden.
Kidney Int
. 2006 May;69(9):1621–5.
22.
Haider I, Anees M, Shahid SA. Restless legs syndrome in end stage renal disease patients on haemodialysis.
Pak J Med Sci
. 2014 Nov-Dec;30(6):1209–12.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.